A technique for label-free detection of proteins resides on the use of surface plasmon resonance (SPR) biosensors. Proteins binding to an immobilized receptor on the SPR sensor results in small, albeit detectable change of refractive index due to the high sensitivity and resolution of SPR to refractive index. Proteins have a relatively large refractive index and are large molecules such that low detection limit in the nM or pM range can be achieved, without labeling the protein. However, SPR microbiosensors have yet to be developed and the optical properties of SPR-active metals, such as gold or silver, are not well characterized at the micrometer scale.
Also, exploitation of thin film SPR has nearly reached theoretical limits. The sensitivity of SPR instruments is identical to theoretical simulations, while the resolution is within the 10−7 RIU (refractive index unit) range.
However, there is still a need for an improved resolution of SPR instruments.